title: Reproducibility of tumor perfusion measurements using 15O-labeled water and PET.
abstract: PET and 15O-labeled water (H215O) can be used to noninvasively monitor tumor perfusion. This allows evaluation of the direct target of antiangiogenic drugs, that is, tumor vasculature. Because these drugs often result in consolidation rather than regression of the tumor mass, a change in perfusion might be a more sensitive way to evaluate response than are indirect size measures on a CT scan. However, to use the technique for serial imaging of individual patients, good reproducibility is essential. The purpose of the present study was to evaluate the reproducibility of quantitative H215O measurements.
  
  
  METHODS
  Nine patients with non-small-cell lung cancer (NSCLC) were scanned twice within 7 d and before any therapy. All H215O scans were followed by an 18F-fluorothymidine scan to allow for adequate volume-of-interest (VOI) definition. VOIs were defined using a 3-dimensional threshold technique. Tumor perfusion and the volume of distribution (VT) were obtained using a 1-tissue-compartment model including an arterial blood volume component and an image-derived input function. The level of agreement between test and retest values was assessed using the intraclass correlation coefficient (ICC) and Bland-Altman analyses. Possible dependency on absolute values and lesion size was assessed by linear regression.
  
  
  RESULTS
  All primary tumors and more than 90% of clinically suspected locoregional metastases could be delineated. In total, 14 lesions in 9 patients were analyzed. Tumor perfusion showed excellent reproducibility, with an ICC of 0.95 and SD of 9%. The VT was only moderately reproducible, with an ICC of 0.52 and SD of 16%. No dependency was found on absolute values of perfusion (P = 0.14) and VT (P = 0.15). In addition, tumor volume did not influence the reproducibility of perfusion (P = 0.46) and VT (P = 0.25).
  
  
  CONCLUSIONS
  Quantitative measurements of tumor perfusion using H215O and PET are reproducible in NSCLC. When patients are repeatedly being scanned during therapy, changes of more than 18% in tumor perfusion and 32% in VT (>1.96 x SD) are likely to represent treatment effects.
authors.affiliation: Department of Respiratory Medicine, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: Adrianus J
authors.initials: AJ
authors.lastname: de Langen
authors.forename: Mark
authors.initials: M
authors.lastname: Lubberink
authors.forename: Ronald
authors.initials: R
authors.lastname: Boellaard
authors.forename: Marieke D
authors.initials: MD
authors.lastname: Spreeuwenberg
authors.forename: Egbert F
authors.initials: EF
authors.lastname: Smit
authors.forename: Otto S
authors.initials: OS
authors.lastname: Hoekstra
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: Lammertsma
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000098:blood supply* / Q000000981:diagnostic imaging*; D006801:Humans; D010104:Oxygen Radioisotopes; D010477:Perfusion; D049268:Positron-Emission Tomography; D015203:Reproducibility of Results; D014867:Water / Q000737:chemistry
chemical_list: D010104:Oxygen Radioisotopes; D014867:Water